Global burden of multidrug-resistant tuberculosis in children and adolescents

Global trends regarding MDR-TB disease burden among children and adolescents

In 2019, a total of 67,710.82 (95% UI: 38823.61–110582.03) cases of MDR-TB in children and adolescents were recorded worldwide. A total of 95,646.65 (95% UI: 54014.64–154776.51) cases of MDR-TB were identified in 2019, resulting in 7061.39 deaths (95% UI: 3180.92–12526.53) and 611246.97 DALYs (95% UI: 283570.45–1069494.83) (Table 1).

The incidence, prevalence, mortality, and DALY rates in 2019 were 2.63 (95% UI: 1.51–4.29), 3.71 (95% UI: 2.09–6.00), 0.27 (95% UI: 0.12–0.49), and 23.7 (95% UI: 10.99–41.46) per 100,000 children and adolescents (<20 years of age). For girls, the incidence, prevalence, mortality, and DALY rates were 3.04 (95% UI: 1.73–4.95), 4.88 (95% UI: 2.68–8.08), 0.29 (95% UI: 0.13–0.53), and 25.32 (95% UI: 11.79–45.67) per 100,000 girls. These values are higher than those for boys. Notably, the EAPC of incidence, prevalence, mortality, and DALY rates for the period 1990–2019 were higher for girls than they were for boys (Table S1).

The mortality and DALY rates in 2019 were higher for children <5 years of age than they were for older age groups, which were 0.62 (95% UI: 0.28–1.14) and 55.19 (95% UI: 25.24–100.74) per 100,000 individuals, respectively (Table S1). The age group of 15–19 years demonstrated a significantly higher incidence rate (5.47 [95% UI: 2.64–10.17] per 100,000) and a higher prevalence rate (5.18 [95% UI: 2.35–9.48] per 100,000) than those shown by the other age groups (Table S1).

The EAPC for the rate of incidence, prevalence, death, and DALYs were 4.15% (95% UI: 1.10–12.19%), 5.45% (95% UI: 1.64–14.74%), 1.49% (95% UI: 0.13–4.98%), and 1.49% (95% UI: 0.14–4.98%), respectively, for the period spanning from 1990 to 2019 (Table 1). A steady increase in incidence rates was observed from 1990 to 2005, followed by a decline from 2005 to 2015. However, a slight rebound has been noted in the past 5 years. The 15–19 year age group demonstrated a significantly higher incidence rate compared to that exhibited by the other age groups (Fig. 1a, Table S2A). The prevalence rates steadily increased from 1990 to 2005, followed by a decline from 2005 to 2015. They have remained relatively stable between 2016 and 2019. The prevalence rates for girls of all age groups were higher than they were for boys (Fig. 1b, Table S2B). The overall mortality rate increased from 0.11 (95% UI: 0.04–0.26) per 100,000 in 1990 to 0.55 (95% UI: 0.24–0.98) per 100,000 in 2001, followed by a gradual decrease to 0.27 (95% UI: 0.12–0.49) per 100,000 in 2019. Notably, the <5-year age group exhibited a higher mortality burden than that shown by the other age groups for the period 1990–2019 (Fig. 1c, Table S2C). The DALY rate trend followed a similar pattern to mortality rates, with the <5-year age group exhibiting higher DALY rates compared to that demonstrated by other age groups during 1990–2019, for both boys and girls (Fig. 1d, Table S2D).

Incidence rate (a), prevalence rate (b), death rate (c), DALY rate (d); MDR‐TB multidrug-resistant tuberculosis, DALY disability-adjusted life year.

MDR-TB disease burden among children and adolescents in GBD super-regions

The MDR-TB burden among children and adolescents varies in GBD super-regions. The top three highest incidence rates in 2019 were recorded in Southern sub-Saharan Africa, Eastern Europe, and South Asia [12.95(95% UI: 6.12–26.95), 5.02(95% UI: 2.99–7.79), and 5.01(95% UI: 1.69–10.85) per 100,000, respectively]. The top three highest rates of deaths and DALYs in 2019 were recorded in Southern, Central, and Eastern sub-Saharan Africa (Table S3).

Between 1990 and 2019, the incidence rate was found to decrease in East Asia, Caribbean, High-income Asia Pacific, and High-income North America. In contrast, the incidence rate increased in the remaining regions, especially in Oceania, Central Asia, and South Asia, which recorded EAPC increases of 70.28% (95% UI: 13.25–408.71%), 62.12% (95% UI: 20.21–206.30%), and 36.81% (95% UI: 6.79–180.78%), respectively (Table S3A). The death rate was observed to decrease in East Asia, High-income Asia Pacific, and High-income North America, while it was nearly zero in Central Europe, Southern Latin America, Western Europe, High-income North America, Australasia, and High-income Asia Pacific. However, a consistent increase in the death rate was observed in the remaining regions and the highest increases were recorded in Oceania, Central Asia, and South Asia, with EAPC increases of 35.31% (95% UI: 5.85–251.29%), 19.01% (95% UI: 6.62–65.14%), and 8.60% (95% UI: 1.23–46.11%) respectively (Table S3B). Overall, the MDR-TB death rate is negatively associated with SDI levels, although the death rate varies among the GBD super-regions at the same SDI level (Table S3B). The DALY rate and trend in the GBD super-regions are similar to their death burden (Table S3C).

We further explored the MDR-TB disease burden and trends related to SDI levels in the GBD super-regions. A negative correlation was found between the incidence rate of MDR-TB and SDI (R = −0.318, P = 0.16) in 2019, although the Southern sub-Saharan Africa had an expected high incidence rate at 12.95 (95% UI: 6.12–26.95) per 100,000 population and an SDI of 0.64 in 2019 (Fig. 2a). The EAPC of the MDR-TB incidence rate from 1990 to 2019 showed a significant negative correlation with the SDI level (R = −0.469, P < 0.05, Fig. 2b). The death rate in 2019 (R = −0.711, P < 0.05) and the EAPC of the death rate from 1990 to 2019 (R = −0.469, P < 0.05) exhibited a significant negative correlation with the SDI level of 2019 (Fig. 2c, d). In addition, the DALY rate in 2019 (R = −0.698, P < 0.05) and the EAPC of the DALY rate from 1990 to 2019 (R = −0.461, P < 0.05) showed a significant negative correlation with the SDI level of 2019 (Fig. 2e, f).

Incidence rate (a), EAPC of incidence rate (b), death rate (c), EAPC of death rate (d), DALY rate (e), and EAPC of DALY rate (f). Correlation was calculated with Pearson correlation analysis. MDR‐TB multidrug-resistant tuberculosis, GBD global burden of disease, SDI sociodemographic index, DALY disability-adjusted life years]

To understand variations in disease burden in the GBD super-regions across different SDIs, the correlation between SDIs and MDR-TB incidence and death rates in the super-regions from 1990 to 2019 was analyzed. Overall, the MDR-TB incidence rate had a significant negative correlation with SDIs (R = −0.196, P < 0.05). For SDIs < 0.7, the incidence rate decreased with increasing SDIs in most of the GBD super-regions, except for Southern sub-Saharan Africa and Central Asia. For SDIs >0.7, the incidence rate of MDR-TB is close to 0 in most regions, except for Eastern Europe. The level of SDIs in the Eastern Europe region gradually changed from 0.68 in 1990 to 0.79 in 2019. The incidence rate rose rapidly from 0.45 (95% UI: 0.17–1.14) per 100,000 in 1990 to 8.39 (95% UI: 4.70–13.38) per 100,000 in 2005, followed by a gradual decrease to 5.02 (95% UI: 2.99–7.79) per 100,000 in 2019 (Fig. 3a, Table S4). A significant negative correlation was observed between the MDR-TB death rate and SDIs (R = -0.609, P < 0.05). However, the death rate in Southern and Central sub-Saharan African regions was higher than the expected SDI level (Fig. 3b, Table S4).

Incidence (a) and death (b) rate of children and adolescents with MDR-TB. Each point in a line represents 1 year, starting from 1990 and ending in 2019. Solid black line shows expected values across the spectrum of the SDI. MDR‐TB multidrug-resistant tuberculosis, GBD global burden of disease, SDI sociodemographic index.

Country-level MDR-TB disease burden among children and adolescents

The top three countries with the highest MDR-TB incidence rate in 2019 were Eswatini at 39.75 (95% UI: 9.12–97.09), Lesotho at 20.04 (95% UI: 6.66–45.24), and Namibia at 15.82 (95% UI: 6.48–31.95) per 100,000. In 2019, 49 countries had an incidence rate of <0.05 per 100,000, accounting for 24.02% of all countries (Fig. 4a, Table S5A). During 2010–2019, the top three countries with the highest EAPC of incidence rate were the Philippines at 2.06% (95% UI: −0.25% to 7.81%), Papua New Guinea at 1.66% (95% UI: -0.34% to 9.45%), and Comoros at 1.62% (95% UI: −0.44% to 11.56%). A total of 67 countries had a positive EAPC of the MDR-TB incidence rate, accounting for 32.84% (Fig. 4b, Table S5B). The MDR-TB incidence rate showed a stable decline in Guam, Hungary, Kazakhstan, Cyprus, Slovenia, and Iceland, with both EAPC and 95% UI < 0 (Fig. 4b, Table S5B).

a MDR‐TB incidence rate in children and adolescents in 2019 in countries/territories; b EAPC of children and adolescents MDR‐TB incidence rate between 2010 and 2019 in countries/territories; c MDR‐TB death rate among children and adolescents afflicted with the disease in 2019. d EAPC of children and adolescents with MDR‐TB incidence rate between 2010 and 2019. e MDR‐TB DALY rate among children and adolescents in 2019. f EAPC of MDR‐TB DALYs rate among children and adolescents with the disease between 2010 and 2019. MDR‐TB multidrug-resistant tuberculosis; EAPC estimated annual percentage change; DALY disability-adjusted life year].

A significantly high MDR-TB death burden among children and adolescents was observed in African countries. The top three countries with the highest death rate were Somalia, Eswatini, and Lesotho in 2019 [3.66 (95% UI: 0.86–9.61), 3.28 (95% UI: 0.74–7.30), and 2.41 (95% UI: 0.65–5.87) per 100,000, respectively]. In 2019, 92 countries had a death rate of nearly 0, accounting for 45.1% of all countries (Fig. 4c, Table S5C). During 2010–2019, the EAPC for the MDR-TB death rate was positive for 23 countries (Fig. 4d, Table S5D).

In 2019, the top three countries with the highest DALY rates for children and adolescents with MDR-TB were Somalia, Eswatini, and Lesotho [308.88 (95% UI: 72.24–811.08), 289.93 (95% UI: 63.68–652.98), and 207.26 (95% UI: 58.64–498.19) per 100,000, respectively] (Fig. 4e, Table S5E). Notably, 21 countries, accounting for 10.29% of all countries that we considered herein, recorded a stable decline in the MDR-TB DALY rate. The top three countries with the highest EAPC of the DALY rate from 2010 to 2019 were Papua New Guinea at 0.88% (95% UI: −0.54% to 6.46%), Bermuda at 0.54% (95% UI: −0.84% to 10.69%), and Dominica at 0.41% (95% UI: −0.77% to 7.44%) (Fig. 4f, Table S5F).